Pompe disease: pathogenesis, molecular genetics and diagnosis

Aging (Albany NY). 2020 Aug 3;12(15):15856-15874. doi: 10.18632/aging.103794. Epub 2020 Aug 3.

PMID: 32745073

Simona Taverna, Giuseppe Cammarata, Paolo Colomba, Serafina Sciarrino, Carmela Zizzo, Daniele Francofonte, Marco Zora, Simone Scalia, Chiara Brando, Alessia Lo Curto, Emanuela Maria Marsana, Roberta Olivieri, Silvia Vitale, Giovanni Duro

Summary: Early detection is critical for preventing or reducing the permanent organ damage that comes with Pompe disease (PD) progression. Pathogenesis, clinical phenotypes, molecular genetics, diagnosis and treatments about PD are covered in this article.

Abstract

Background: Pompe disease (PD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, which codes for acid alpha-1,4-glucosidase (GAA) and is localized on chromosome 17. More than 560 mutations have been discovered in the GAA gene to date. GAA catalyzes the hydrolysis of α-1,4 and α-1,6-glucosidic bonds of glycogen, and its absence causes lysosomal glycogen accumulation in a variety of tissues, especially in muscle. PD is a chronic, progressive disease marked by limb-girdle muscle weakening and respiratory failure. There are two types of PD: infantile and childhood/adult forms.

Objective: Patients with PD have a multisystemic presentation that varies depending on the age of onset. Early detection is critical for preventing or reducing the permanent organ damage that comes with PD progression. Pathogenesis, clinical phenotypes, molecular genetics, diagnosis, treatments, autophagy, and the significance of miRNAs as potential biomarkers for PD are all covered in this article.

Keywords: GAA; Pompe disease; acid alpha-1,4-glucosidase; glycogen; lysosomal storage disorder.